N1-(5-chloropyridin-2-yl)-N2-(4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide represented by the following formula (I):
or a pharmacologically acceptable salt thereof, or a solvate thereof (in the present specification, the compound represented by formula (I) is referred to as compound I, and compound I, a pharmacologically acceptable salt thereof, and solvates thereof are also collectively referred to as compound I, etc.) is known to exhibit a potent inhibitory effect on activated blood coagulation factor X (activated factor X; hereinafter, also referred to as FXa in the present specification) and be useful as a pharmaceutical drug, particularly, an activated blood coagulation factor X inhibitor (hereinafter, also referred to as an FXa inhibitor or anti-FXa in the present specification) and/or an agent for preventing and/or treating thrombosis or embolism (Patent Documents 1 to 4).
Compound I is a basic compound that exhibits favorable solubility in a strongly acidic aqueous solution, but reduced solubility in a neutral aqueous solution (e.g., a neutral buffer). A pharmaceutical composition containing compound I, etc. as an active ingredient also exhibits poor dissolution properties of compound I, etc. in a neutral aqueous solution. A method comprising coating a composition containing compound I, etc. with one or two or more coating agents selected from a cellulose derivative, a polyvinyl compound, an acrylic acid derivative, and a saccharide is known as a method for improving the dissolution properties of compound I, etc. in the neutral region of a solid pharmaceutical composition containing compound I, etc. as an active ingredient (Patent Document 4). Patent Document 4 discloses a pharmaceutical composition wherein the content of compound I is 15% by weight with respect to the total weight of the pharmaceutical composition.
Citation List
    Patent Document    Patent Document 1: WO 2003/000657    Patent Document 2: WO 2003/000680    Patent Document 3: WO 2003/016302    Patent Document 4: WO 2008/129846